COMT enzyme characteristics (Km, V, ratio of meta/paramethylation) were determined in the red blood cells of 20 patients with endogenous depression, in 20 healthy controls matched as to age and sex, as well as in 10 patients with mania, and 10 patients with neurotic depression. Assessment was done twice, i.e. before and after remission in patients with endogenous depression and in the manic patients. If male and female patients are considered together there was no statistical difference between the COMT characteristics of these patient groups, either before or after remission. Only the bipolar patients showed a higher COMT-activity (V) than their individually matched controls. If however, only the female patients are taken into consideration, COMT-activity of the patients with endogenous depression vs. controls is significantly increased by 60%. This difference can be demonstrated also after remission ("free interval") though statistical significance is reached only for the unipolar group. Further in vitro experiments indicate that antidepressant drugs do not possess a relevant influence on COMT-activity. Ranking the mean COMT-values leads to the following order: matched controls (< neurotic depression < unipolar depression < bipolar depression, which would be in good agreement with theoretical expectations based on the amine hypothesis of depression. Compared with normal male subjects COMT-activity of female controls is significantly lower. On the other hand, the female patients with endogenous depression show a significantly higher enzyme activity than the corresponding male patients.